The specific goals of the grant are: a. To define the acute toxicities of new anticancer agents in patients with advanced cancer. b. To re-define the acute toxicities and pharmacokinetics of existing anticancer agents administered in combination with colony stimulating factors and other toxicity-ameliorating agents which may facilitate the exploration of more effective doses and schedules. c. To provide information on the pharmacologic characteristics (absorption, distribution, metabolism, and elimination) of selected antitumor agents. d. To define treatment regimens for evaluation of antitumor activity in Phase II trials. e. Based on pharmacologic characteristics, to establish appropriate Phase II doses in special patient populations, such as those with impaired end- organ function or with heavy pretreatment, geriatric populations, and to explore pharmacokinetic and pharmacodynamic differences based on gender, race or ethnic group. f. To obtain preliminary information on pharmacokinetic/pharmacodynamic correlations with can then be extended in Phase II trials. g. To incorporate ancillary basic laboratory studies, when possible and appropriate, to enhance our understanding of the biochemical and/or biological mechanisms of drug actions. The agents to be studied will include the following: a. Cytotoxic chemotherapeutic agents identified by the NCIs drug screening program. b. Cytotoxic agents with novel mechanisms, including antiangiogenesis agents, differentiating agents, apoptosis-inducing agents, anti-sense oligonucleotides and related gene-specific therapeutic agents, and targeted cytoxic agents. C. Existing chemotherapeutic agents which, when administered with colony stimulating factors or other agents to ameliorate dose-limiting toxicities, can be given in doses substantially higher than those previously tested. d. Agents developed by the pharmaceutical industry and provided to the NCI for collaborative development. This grant shall accrue at least 25-50 patients per year to at least three active phase I trials per year for five years. Pharmacokinetics and/or correlative lab studies shall be a standard feature of these studies. Pharmacokinetics will be assessed in an ongoing manner in proximity to treatment rather than in a batched manner to facilitate incorporation of pharmacokinetic data in dosing decision-making. Some phase I studies of combination and/or modulation studies may not require intensive pharmacokinetic data collection and this, as well as the credit to be assigned, will be determined at the time of the Letter of intent (LOI) review or protocol review by program staff.